Perfil proteômico hipocampal em epilepsia do lobo temporal

In this study we used proteomics approaches to obtain the protein profile of human epileptic hippocampi (N=6) and control hippocampi obtained from autopsy (N=6). We used two-dimensional gel electrophoresis (2-D) coupled to HPLC and Mass spectroscopy (MALDI-TOF) to identify proteins differentially expressed. Nine proteins were differentially expressed comparing the hippocampus of patients with the hippocampus of control. Proteins that were increased in the hippocampus of patients with TLE were: isoform 1 of serum albumin, HSP 70, dihydropyrimidinase-related protein 2, isoform 1 of myelin basic protein, proton ATPase catalytic subunit A, and dihydrolipoyllysine-residue acethyltransferase component of pyruvate dehydrogenase complex. The expression of isoform 3 of spectrin alpha chain (fodrin) was down-regulated while the proteins glutathione S-transferase P and the DJ-1 (PARK7) were detected only in the hippocampus of patients with TLE. Taken together, our results provide evidence supporting a direct link between metabolic disturb and oxidative damage related to pathophysiology of TLE. Besides, indicates biomarkers for further investigations as therapies targeted to epilepsy.No presente estudo empregou-se o método de proteômica para obter a expressão diferencial de proteínas em hipocampo de pacientes com epilepsia do lobo temporal (ELT) (N=6) comparado a hipocampos controle obtidos por meio de autópsia (N=6). O estudo foi feito por meio de eletroforese bidimensional, acoplada a HPLC e espectroscopia de massa. As proteínas que tiveram expressão aumentada no hipocampo de pacientes com ELT foram: isoforma-1 da soroalbumina, HSP70, diidropirimidinase-2, isoforma-1 da proteína básica da mielina, subunidade catalítica A da próton ATPase, glutationa S-transferase P, proteína DJ-1 (PARK7), e resíduo diidropolilisina do componente acetil-transferase do complexo da piruvato desidrogenase. A expressão da isoforma-3 da cadeia alfa da espectrina (fodrina) foi menor no hipocampo de pacientes com epilepsia do lobo temporal e as proteínas glutationa S-transferase P e PARK7 foram detectadas somente no tecido epiléptico. Assim, nossos resultados trazem evidencias sobre a direta relação entre distúrbio metabólico e dano oxidativo na patofisiologia da ELT. Além disto, o estudo indica biomarcadores para futuras investigações como alvos terapêuticos para epilepsia.UNIFESP Departamento de Neurologia e NeurocirurgiaUNIFESP Departamento de Microbiologia, Imunologia e ParasitologiaFaculdade de Medicina da Universidade de São Paulo Instituto do Coração Departamento de Anatomia PatológicaUNIFESP, Depto. de Neurologia e NeurocirurgiaUNIFESP, Depto. de Microbiologia, Imunologia e ParasitologiaSciEL

Carbamazepine inhibits angiotensin I-converting enzyme, linking it to the pathogenesis of temporal lobe epilepsy

We find that a common mutation that increases angiotensin I-converting enzyme activity occurs with higher frequency in male patients suffering from refractory temporal lobe epilepsy. However, in their brains, the activity of the enzyme is downregulated. As an explanation, we surprisingly find that carbamazepine, commonly used to treat epilepsy, is an inhibitor of the enzyme, thus providing a direct link between epilepsy and the renin-angiotensin and kallikrein-kinin systems. Translational Psychiatry (2012) 2, e93; doi:10.1038/tp.2012.21; published online 13 March 2012INNTConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo, Dept Biophys, BR-04023032 São Paulo, BrazilUniversidade Federal de São Paulo, BR-04023032 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Pathol, BR-04023032 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Neurol & Neurosurg, BR-04023032 São Paulo, BrazilUniv São Paulo, Sch Arts Sci & Humanities, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Sci & Technol, BR-04023032 São Paulo, BrazilNove de Julho Univ UNINOVE, Dept Rehabil Sci, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biophys, BR-04023032 São Paulo, BrazilUniversidade Federal de São Paulo, BR-04023032 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Pathol, BR-04023032 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Neurol & Neurosurg, BR-04023032 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Sci & Technol, BR-04023032 São Paulo, BrazilWeb of Scienc

Avaliação clínica e tratamento cirúrgico de pacientes com tumores cerebrais indolentes e epilepsia

INTRODUCTION: In this study the authors review the outcomes of 22 patients with medically refractory epilepsy and slow growth brain tumors. OBJECTIVES: Evaluate the clinical, electrophysiological, operative, and histopathological features. PATIENTS AND RESULTS: The majority of the tumors were located in the temporal lobe (n = 20) and involved the cortical gray matter. The most frequent tumors were gangliogliomas (n = 9), astrocytomas grade I and II (n = 6), dysembryoplastic neuroepithelial tumors (n = 5) and ganglioneuroma (n = 2). The biological behavior of the tumors was strikingly indolent, as indicated by a long preoperative history of chronic seizures (mean, 14 years). Mean follow-up time after resection was 27 months, and according to Engel s classification, 85% were seizure-free, 10% showed a reduction of seizure frequency of at least 90%, and 5% had reduction in seizure frequency at least 75%. CONCLUSION: The data indicate that neoplasms associated with pharmacoresistent epilepsy constitute a distinct clinicopathological group of tumors that arise in young patients, involve the cortex, and exhibit indolent biological behavior for many years. Complete surgical removal of these tumors, including the epileptogenic area, can achieve excellent seizure control.INTRODUÇÃO: Neste estudo os autores avaliaram retrospectivamente 22 pacientes tratados cirurgicamente com diagnóstico de epilepsia refratária e tumor cerebral de crescimento lento. OBJETIVOS: Avaliar os aspectos clínicos, eletrofisiológicos, cirúrgicos e histopatológicos. PACIENTES E RESULTADOS: A maioria dos tumores estava localizada no lobo temporal (n = 20) com envolvimento da substância cinzenta. Ganglioglioma foi o tumor mais frequente (n = 9), seguido do astrocitoma grau I e II OMS (n = 6), tumor neuroepitelial disembrioplástico (DNET) (n = 5) e ganglioneuroma (n = 2). O comportamento biológico dos tumores foi estritamente indolente como indicado pela longa história pré-operatória de (média, 14 anos). O tempo de acompanhamento pós-operatório médio foi de 27 meses e de acordo com a Classificacão de Engel, 85% ficaram sem crises (Classe I), 10% obtiveram redução maior de 90% das crises (Classe II), e 5% tiveram redução menor que 75% (Classe III). CONCLUSÃO: Os dados indicam que neoplasias associadas à epilepsia crônica refratária constituem um grupo de tumores com características clinico-patológicas distintas que se iniciam em pacientes jovens, envolvem o córtex e apresentam comportamento biológico indolente. A ressecção cirúrgica completa destes tumores, incluindo a zona epileptogênica, levou ao controle total das crises na maior parte dos casos estudados.Universidade Federal de São Paulo (UNIFESP) Unidade de Pesquisa e Tratamento das Epilepsias Departamentos de Neurologia e Neurocirurgia, Patologia e Diagnóstico por ImagemUNIFESP, Unidade de Pesquisa e Tratamento das Epilepsias Depto.s de Neurologia e Neurocirurgia, Patologia e Diagnóstico por ImagemSciEL

Correlation between temporal pole MRI abnormalities and surface ictal EEG patterns in patients with unilateral mesial temporal lobe epilepsy

Objective: the objective of this retrospective study is to analyze ictal patterns observed during continuous Video-EEG monitoring in patients with temporal Lobe epilepsy (TLE) due to unilateral hippocampal sclerosis (HS), and to correlate these EEG patterns to temporal pole abnormalities observed on magnetic resonance imaging exams.Methods: We analyzed 147 seizures from 35 patients with TLE and unilateral HS. Ictal patterns were classified.,and correlated to signal abnormalities and volumetric measures of the temporal poles. Volume differences over 10% were considered abnormal.Results: the most frequent type of ictal pattern was rhythmic theta activity (RTA), encountered in 65.5% of the seizures. Rhythmic beta activity (RBA) was observed in 11% of the seizures, localized attenuation in 8%, interruption of epileptiform discharges in 6%, repetitive discharges in 5.5%, and rhythmic delta activity (RDA) in 4%. Sixty-six percent of the patients presented signal abnormalities in the temporal pole that were always ipsitateral to the HS. Sixty percent presented significant asymmetry of the temporal poles consisting of reduced volume that was also always ipsitateral to HS. Although patients with RTA as the predominant ictal pattern tended to present asymmetry of temporal poles (p = 0.305), the ictal EEG pattern did not correlate with temporal pole asymmetry or signal abnormalities.Conclusions: RTA is the most frequent initial ictal pattern inpatients with TLE due to unilateral HS. Temporal pole signal changes and volumetric reduction were commonly found in this group of patients, both abnormalities appearing always ipsitateral to the HS. However, neither temporal pole volume reduction nor signal abnormalities correlated with the predominant ictal pattern, suggesting that the temporal poles are not crucially involved in the process of epileptogenesis. (c) 2006 British Epilepsy Association. Published by Elsevier B.V. All rights reserved

Auras somatossensoriais em epilepsia mesial temporal: características semiológicas, achados neurorradiológicos e diagnóstico diferencial com epilepsia de lobo parietal

INTRODUCTION: Somatosensory auras (SSAs) are more usually described in patients with parietal lobe epilepsy (PLE), producing more commonly a localized cutaneous tingling sensation, involving hands and fingers followed by tonic or clonic focal seizures. These usually originate in the contralateral hemisphere. Etiology includes dysplasias, tumours, ischemic or postencephalitic gliosis. However, other focal epilepsies, such as frontal and temporal, may also originate SSAs. Although this type of aura is reported as rare in patients with mesial temporal lobe epilepsy (MTLE), this association has not been systematically studied. OBJECTIVES: The aim of this article was to describe the cases of four patients with refractory MTLE and SSAs, reporting their clinical characteristics and MRI findings. We discuss the localizing and lateralizing value of SSAs, particularly in the context of MTLE. METHODS AND RESULTS: Four patients with refractory MTLE and SSAs followed-up in the outpatient's clinic at the Epilepsy Section, Universidade Federal de São Paulo (UNIFESP), were submitted to presurgical evaluation and corticoamygdalohippocampectomy. MRI in all cases showed unilateral mesial temporal sclerosis (MTS). Regarding seizure semiology, tingling sensation involving the upper extremity was the most prevalent symptom. Three of the four patients had SSAs contralateral to the MTS. Following the SSAs all patients most of the time presented other symptoms such as autonomic or psychic auras evolving to psychomotor seizures. After surgical treatment, two of the patients presented infrequent auras, and two were rendered seizure-free. CONCLUSION: Although rare, SSAs can be present in MTLE. The characteristics of autonomic or psychic auras, psychomotor seizures, neuropsychological deficits, and typical neurophysiologic and MRI findings may help differentiate patients with MTLE from those with PLE.INTRODUÇÃO: Auras somatossensoriais (AS) são mais frequentemente descritas em pacientes com epilepsia de lobo parietal (ELP), produzindo sensação de formigamento cutâneo envolvendo mão e dedos seguida de sinais motores focais tônicos ou clônicos. Estas crises habitualmente originam-se no hemisfério cerebral contralateral. Displasias, tumores, patologias vasculares ou gliose pós encefalite constituem as etiologias mais prováveis. Outras epilepsias focais, como as de lobo frontal e temporal podem também originar (AS). Embora este tipo de aura seja considerada rara em pacientes com epilepsia mesial do lobo temporal (EMLT), esta associação ainda não foi sistematicamente estudada. OBJETIVOS: A proposta deste artigo foi descrever quatro casos de EMLT refratária ao tratamento clínico, apresentando AS, reportar as características clínicas comuns, achados de neuroimagem e estudar o valor localizatório e lateralizatório das mesmas. MÉTODOS E RESULTADOS: Quatro pacientes com EMLT refratária e AS acompanhados no ambulatório de Epilepsia, Universidade Federal de São Paulo (UNIFESP), foram submetidos a avaliação pré-cirúrgica. Sensação de formigamento envolvendo a extremidade superior foi o sintoma predominante em todos. Em três (75%) as auras foram contralaterais à esclerose mesial temporal (EMT). Em todos as AS eram, com maior freqüência, seguidas por outras auras autonômicas e psiquícas e evoluiam para crises parciais complexas (crises psicomotoras). CONCLUSÃO: Embora raras, AS podem estar presentes em EMLT. A associação de auras autonômicas e psíquicas, presença de crises parciais complexas (psicomotoras), déficits neuropsicológicos distintos, além de achados neurofisiológicos e de neuroimagem podem diferenciar pacientes com EMLT daqueles com ELP.Universidade Federal de São Paulo (UNIFESP) Departmento de Neurologia e Neurocirurgia Unidade de Pesquisa e Tratamento de EpilepsiasUniversidade Federal de São Paulo (UNIFESP) Departmento de Neurologia e NeurocirurgiaUniversidade Federal de São Paulo (UNIFESP) Divisão de Neurorradiologia Departmento de RadiologiaUNIFESP, Departmento de Neurologia e Neurocirurgia Unidade de Pesquisa e Tratamento de EpilepsiasUNIFESP, Departmento de Neurologia e NeurocirurgiaUNIFESP, Divisão de Neurorradiologia Departmento de RadiologiaSciEL